Tunicamycin protein

The oligosaccharide GICjMangCGIcNAcjj is transferred from dolichol-P-P-oligosaccharide in a reaction catalyzed by oligosaccharide protein transferase, which is inhibited by tunicamycin. 

Glycosyladon of the p62 afad El proteins is not needed for correct assembly in the ER, since in tunicamycin-treated cells, the assembly of these nonglycosylated proteins proceeds normally (Garoff and Schwarz, 1978). The drug tunicamycin blocks the assembly of the dolichol-linked oligosaccharide intermediate so that no transfer of oligosaccharides to nascent protein is possible (Tkasz and Lampen, 1975). 

Secretion of nonglycosylated macromolecules in the presence of tunicamycin has also been investigated in a number of other cells. Rat-liver cell-secretion ol albumin (a carbohydrate-free protein), transferrin, and a-acid glycoprotein was not inhibited, and, in chick-liver cells, only a decrease by 10-25% in the secretion of transferrin and the apoprotein B chain of very-low-density lipoprotein was noted.463,464 The secretion of ovalbumin (a glycoprotein) from hen oviduct was not blocked by tunicamycin.465... 

Inhibition of glycosylation was shown to interfere with certain stages of development, as shown in the previous examples. However, in cultured, human and myeloid leukemia cells, tunicamycin treatment induced differentiation. From this observation, it has been concluded that glycosylation of cellular proteins plays a role in maintaining these cells in a transformed stated"... 

A notable finding was the defective transport of D-glucose, uridine, and two amino acid analogs (2-aminobutanoate and cycloleucine) in chick-embryo cells in which glycosylation of proteins was prevented by tunicamycin. Other membrane-associated processes, such as the enzymic activities of Na/K ATPase and adenylate cyclase, or the stimulation of adenylate cyclase by a prostaglandin and cholerae toxin, were not affected.546... 

Tunicamycins] (uridine glycosides) Streptomyces spp. (fungi) Apoptotic (jV-linked protein glycosylation inhibitors)... 

Several compounds effectively inhibit Pgp, competitively or noncompetitively. These include verapamil, R-verapamil, cyclosporin-A, PSC 833, LY 335979, GF 120918, S 9788, and RU-486 (82). Another possibility for interaction with Pgp is at its glycosylation sites. Pgp has three glycosylation sites however, blocking of these sites with tunicamycin did not change its efflux function (83). In addition, there are various phosphorylation sites at Pgp that are phosphorylated by protein kinase A and C (84). Application of protein kinase C (PKC) inhibitors resulted in increased accumulation of Pgp substrates (85), whereas phorbol esters stimulated its phosphorylation and increased drug resistance (86). However, the problem with PKC inhibitors is that these compounds are not specific for one PKC isoenzyme. In addition, the PKC inhibitor bryostatin leads first to activation of PKC and later to a downregulation of PKC. For these reasons, PKC modulation has led to many contradicting results (87). 

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